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Preparation, <i>In-vitro, Ex-vivo</i>, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based <i>In Situ</i> Gel
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Background:

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.

Objective:

This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.

Method:

Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.

Result:

The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.

Conclusion:

NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

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The art of adornment and make-up in the ancient civilizations of Mesopotamia and the old country of Yemen as a model
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This research sheds light on those discrepancies in the use of ornaments, adornment and perfumes, as well as the art of cosmetics, in two important civilizations, namely, the Mesopotamian civilization as the earlier civilization, and the civilization of Yemen, which represents the first Arab civilization. Through the foregoing, our research includes two topics, the first topic included the history of the use of decorations, ornaments and perfumes in the civilization of Mesopotamia, while the second topic included the study of ornaments, adornment and cosmetic art in the ancient civilization of Yemen. And then the research came out with a number of conclusions that the researcher considers very important to highlight the differences and f

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Mon Jan 01 2018
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Liquid Chromatographic and validation study in separation and determination of benzidines and phenols in the main discharge point of wastewater
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Optimal UAV Deployment for Data Collection in Deadline-based IoT Applications
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The deployment of UAVs is one of the key challenges in UAV-based communications while using UAVs for IoT applications. In this article, a new scheme for energy efficient data collection with a deadline time for the Internet of things (IoT) using the Unmanned Aerial Vehicles (UAV) is presented. We provided a new data collection method, which was set to collect IoT node data by providing an efficient deployment and mobility of multiple UAV, used to collect data from ground internet of things devices in a given deadline time. In the proposed method, data collection was done with minimum energy consumption of IoTs as well as UAVs. In order to find an optimal solution to this problem, we will first provide a mixed integer linear programming m

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Priority Based Transmission Rate Control with Neural Network Controller in WMSNs
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Wireless Multimedia Sensor Networks (WMSNs) are networks of wirelessly interconnected sensor nodes equipped with multimedia devices, such as cameras and microphones. Thus a WMSN will have the capability to transmit multimedia data, such as video and audio streams, still images, and scalar data from the environment. Most applications of WMSNs require the delivery of multimedia information with a certain level of Quality of Service (QoS). This is a challenging task because multimedia applications typically produce huge volumes of data requiring high transmission rates and extensive processing; the high data transmission rate of WMSNs usually leads to congestion, which in turn reduces the Quality of Service (QoS) of multimedia applications. To

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Performance Evaluation Based on Multi-UAV in Airborne Computer Network System
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Alternative Risk Models for Optimal Investment in Portfolio-Based Community Solar
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Sun Apr 01 2018
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An intersection-based segment aware algorithm for geographic routing in VANETs
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In networking communication systems like vehicular ad hoc networks, the high vehicular mobility leads to rapid shifts in vehicle densities, incoherence in inter-vehicle communications, and challenges for routing algorithms. It is necessary that the routing algorithm avoids transmitting the pockets via segments where the network density is low and the scale of network disconnections is high as this could lead to packet loss, interruptions and increased communication overhead in route recovery. Hence, attention needs to be paid to both segment status and traffic. The aim of this paper is to present an intersection-based segment aware algorithm for geographic routing in vehicular ad hoc networks. This algorithm makes available the best route f

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Bionics-Based Approach for Object Tracking to Implement in Robot Applications
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In this paper, an approach for object tracking that is inspired from human oculomotor system is proposed and verified experimentally. The developed approach divided into two phases, fast tracking or saccadic phase and smooth pursuit phase. In the first phase, the field of the view is segmented into four regions that are analogue to retinal periphery in the oculomotor system. When the object of interest is entering these regions, the developed vision system responds by changing the values of the pan and tilt angles to allow the object lies in the fovea area and then the second phase will activate. A fuzzy logic method is implemented in the saccadic phase as an intelligent decision maker to select the values of the pan and tilt angle based

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Priority Based Transmission Rate Control with Neural Network Controller in WMSNs
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The effectiveness of change and transformation of formal displacement in the internal space (historical passenger stations as a model)
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Intellectual and material displacement is one of the design strategies through many mechanisms and means, and depends on the idea of changing the shape within the internal spaces at times and has concepts related to the transformation at other times. And represented by the boxes for travelers, the research problem emerged through the following question: (What is the effectiveness of displacement in the formal structures in the interior design of historical sites), and the aim of the study is to reveal the reality of the use of historical internal spaces and to determine the formal displacement that occurs as a result of change and transformation, and it included two topics, the first topic Transformation and the effectiveness of formal d

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